Apparatus for stirring liquid materials, including culture mediums, have long been known, particularly stirrer apparatus in which a motor, within a housing, is used to rotate a magnet beneath a platform formed on the housing. On the platfrom, there is a flask having liquid in it, such as liquid culture medium, and a magnet is positioned in the liquid culture medium, and is caused to rotate by the motor-driven magnet in the housing, due to magnetic coupling between the driving magnet and the driven magnet. These magnetic stirrers may generally be classified into two types.
A first type has a cap or top on the flask or other vessel, and the driven magnet is supported by or from this cap or top. Examples of such top-supported driven magnets are as follows. Jacobs, U.S. Pat. No. 2,932,493 discloses a stirrer in which the driven magnet is suspended form the top by a chain or a rod, and is positioned slightly above the bottom of the vessel. Harker, U.S. Pat. No. 3,572,651, provides a flask for stirring a suspension culture of cells in a medium of nutrient substances, includes a magnet supported by a shaft, the shaft being held by a bearing supported by the top or cap of the vessel. Mazowski, U.S. Pat. No. 3,622,129, discloses a construction in which a shaft having a magnet at its lower end extends through or is supported in a bearing in the top or cap. Balas, U.S. Pat. No. 3,854,704, provides a construction in which a stirrer includes a magnet supported by a flexible rod which extends through a stopper of a cell culture container.
A second type of magnetic stirrer apparatus has the driven magnet supported by the bottom of the vessel in which the liquid is contained. Hendricks, U.S. Pat. No. 2,459,224, discloses a stirrer apparatus which includes a magnet at the lower end of a shaft, which rests on the bottom of a container, the shaft having a disc-type agitator fixed to it; rotation of the magnet causes rotation of the shaft and agitator. Steel, U.S. Pat. No. 3,245,665, provides a mixing bar which includes an encapsulating body having a pair of permanent bar magnets embodied in it, and intended to rest on the bottom of a flask and to be rotated by a suitable driven magnet. Bender, U.S. Pat. No. 4,162,855, includes a magnetic rotor mounted within a positioning cage which positions the rotor at the bottom of the vessel; the cage is providedd with bearings for rotatably supporting a magnet.
As an alternative construction to the above-noted provision of a rotating magnet beneath a platform, there has been disclosed an arrangement in which a plurality of static electro-magnets are arranged in a horizontal plane, and circuitry is provided for energizing them in a desired sequence, so as to provide a rotating magnetic field, without actually moving any of the magnets. Such construction is disclosed in Review of Scientific Instruments, March, 1982, pages 369-370, in an article entitled Direct Drive Magnetic Stirrers by chan-Lon Yang and Tzu-Nim Su.
As above noted, it has been recognized that magnetic stirrers are useful in connection with cell culture medium. A survey of the state of this art is found in the article Stirrers for Suspension Cell Cultures by N. A. deBruyne and B. J. Morgan, American Laboratory, June, 1981. That article, among other disclosures, discusses that horizontal rotation of the liquid cell culture medium will not itself cause suspension of particles, but that suspension requires a vertical motion of the liquid. It is also disclosed that where the bearing or support for the shaft is in the top or cap of the vessel or flask, the liquid medium will gradually creep up the rotating vertical shaft and dry out in the bearing. On the other hand, circulation through the bearings, or between a bottom-supported magnet and the bottom, will result in crushing of the particles and microcarriers, if they are used. Microcarriers are tiny solid beads, which are added in large numbers to the nutrient liquid medium, thereby to increase the surface area in the flask, this technique being used in the cultivation of so-called "anchorage dependent cells" which require large areas of solid surface. The noted article also discloses the construction of a flask, known as the Pearson flask, which is characterized by a small conical projection located centrally in the bottom wall of the flask or vessel, which is used in combination with a stirrer suspended from a bearing on the underside of the top or cap of the vessel, on the same axis as the conical projection, the lower end of the stirrer being bulbous and extending into the trough formed between the conical projection and the vertical, cylindrical walls of the flask. The Pearson flask has been found to give the above noted secondary circulation, thereby providing, by definition, vertical motion of the particles, with enhanced culture activity.
Another relevant article is Microcarrier Cell Culture Principles & Methods, published by Pharmacia Fine Chemicals AB, Sweden, 1981. This article discloses a number of rod type stirrers, including the above described Pearson flask with rod stirrer having a bulbous end in the trough.